| First Author | Peng IC | Year | 2012 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 302 |
| Issue | 12 | Pages | E1560-8 |
| PubMed ID | 22454291 | Mgi Jnum | J:187027 |
| Mgi Id | MGI:5435135 | Doi | 10.1152/ajpendo.00504.2011 |
| Citation | Peng IC, et al. (2012) Glucagon regulates ACC activity in adipocytes through the CAMKKbeta/AMPK pathway. Am J Physiol Endocrinol Metab 302(12):E1560-8 |
| abstractText | Glucagon is important for regulating lipid metabolism in part through its inhibition of fatty acid synthesis in adipocytes. Acetyl-CoA carboxylase 1 (ACC1) is the rate-limiting enzyme for fatty acid synthesis. Glucagon has been proposed to activate cAMP-dependent protein kinase A (PKA), which phosphorylates ACC1 to attenuate the lipogenic activity of ACC1. Because AMP-activated protein kinase (AMPK) also inhibits fatty acid synthesis by phosphorylation of ACC1, we examined the involvement of AMPK and its upstream kinase in the glucagon-elicited signaling in adipocytes in vitro and in vivo. LC-MS-MS analysis suggested that ACC1 was phosphorylated only at Ser(79), an AMPK-specific site, in glucagon-treated adipocytes. Pharmacological inhibitors and siRNA knockdown of AMPK or PKA in adipocytes demonstrate that glucagon regulates ACC1 and ACC2 activity through AMPK but not PKA. By using Ca(2+)/calmodulin-dependent protein kinase kinase-beta knockout (CaMKKbeta(-/-)) mice and cultured adipocytes, we further show that glucagon activates the CaMKKbeta/AMPK/ACC cascade. Additionally, fasting increases the phosphorylation of AMPK and ACC in CaMKKbeta(+/+) but not CaMKKbeta(-/-) mice. These results indicate that CaMKKbeta/AMPK signaling is an important molecular component in regulating lipid metabolism in adipocytes responding to glucagon and could be a therapeutic target for the dysregulation of energy storage. |
